Ablating ErbB4 in PV neurons attenuates synaptic and cognitive deficits in an animal model of Alzheimer's disease

Accumulation of amyloid beta (A beta) induces neuronal, synaptic, and cognitive deficits in patients and animal models of Alzheimer's disease (A beta). The underlying mechanisms, however, remain to be fully elucidated. In the present study, we found that A beta interacted with ErbB4, a member of the receptor tyrosine kinase family and mainly expressed in GABAergic intemeurons. Deleting ErbB4 in parvalbumin-expressing neurons (PV neurons) significantly attenuated oligomeric A beta-induced suppression of long term potentiation (LTP). Furthermore, specific ablation of ErbB4 in PV neurons via Cre/loxP system greatly improved spatial memory and synaptic plasticity in the hippocampus of hAPP-J20 mice. The deposition of A beta detected by 3D6 and Thioflavin S staining and the proteolytic processing of hAPP analyzed by western blotting were not affected in the hippocampus of hAPP-J20 mice by deleting ErbB4 in PV neurons. Our data suggested that ErbB4 in PV neurons mediated A beta-induced synaptic and cognitive dysfunctions without affecting A beta levels. (C) 2017 Elsevier Inc. All rights reserved.